Test Catalog

Test ID: THEVP    
Thalassemia and Hemoglobinopathy Evaluation

Useful For Suggests clinical disorders or settings where the test may be helpful

Extensive and economical diagnosis and classification of hemoglobinopathies or thalassemia including complex disorders

 

Evaluation of microcytosis

 

Diagnosis of hereditary persistence of hemoglobin (HPFH)

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This is a consultative evaluation in which the case will be evaluated at Mayo Clinic Laboratories, the appropriate tests performed at an additional charge, and the results interpreted.

 

This evaluation will always include hemoglobin A(2) and F and hemoglobin electrophoresis utilizing cation exchange HPLC and capillary electrophoresis methods.

 

If a serum sample is received, a serum ferritin will always be performed to allow incorporation of possible iron deficiency into profile interpretation and economical test utilization. If the ferritin component is not desired, do not send a serum sample and none will be performed or charged. Fill out the Thalassemia/Hemoglobinopathy Patient Information sheet (T358) and indicate the CBC values and ferritin levels for a more complete evaluation.

Note: If a ferritin is not done or provided, and if microcytosis is present and no other abnormalities are found, the case will be reflexed to alpha-globin gene analysis.

 

Hemoglobin electrophoresis reflex testing, performed at additional charge, may include any or all of the following as indicated to identify rare hemoglobin variants present: sickle solubility (hemoglobin S screen), hemoglobin heat and isopropanol stability studies (unstable hemoglobin), isoelectric focusing, intact globin chain mass spectrometry (hemoglobin variant by mass spectrometry), Hb F distribution by flow cytometry (hemoglobin F red cell distribution), DNA (Sanger) testing for beta chain variants and the most common beta thalassemias (beta-globin gene sequencing), multiplex ligation-dependent probe amplification (MLPA) testing for beta cluster locus large deletions and duplications, including large deletional hereditary persistence of fetal hemoglobin (HPFH), delta-beta (DBT), delta thalassemias, gamma-delta-beta (GDBT), and epsilon-gamma-delta-beta (EGDBT) thalassemias (beta globin cluster locus del/dup), large deletional alpha thalassemias and alpha gene duplications (alpha-globin gene analysis), alpha chain variants and non-deletional alpha thalassemias (alpha-globin gene sequencing), and gamma chain variants and non-deletional HPFH (gamma-globin full gene sequencing).

 

If a Thalassemia/Hemoglobinopathy Patient Information sheet (T358) is received with the sample, the reported clinical features or clinical impression will be considered in the interpretation and focus of the evaluation. Our laboratory has extensive experience in hemoglobin variant identification and many cases can be confidently classified without molecular testing. However, molecular confirmation is always available. If no molecular testing or, conversely, specific molecular tests are desired, please utilize the appropriate check boxes in the information sheet. If the information sheet or other communication is not received, the reviewing hematopathologist will select appropriate tests to sufficiently explain the clinical impression or reported CBC results, which may or may not include molecular testing.

 

Thalassemia Summary Interpretation, an additional consultative interpretation that summarizes all testing, will be provided after test completion to incorporate subsequent results into overall evaluation if any of the following molecular tests are reflexed on the Thalassemia and Hemoglobinopathy Evaluation:

-ATHAL / Alpha-Globin Gene Analysis

-WASQR / Alpha-Globin Gene Sequencing, Blood

-WBSQR / Beta-Globin Gene Sequencing, Blood

-WBDDR / Beta-Globin Cluster Locus Deletion/Duplication, Blood

-WGSQR / Gamma-Globin Full Gene Sequencing

 

See Benign Hematology Evaluation Comparison in Special Instructions.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

This consultative study has the ability to test for the detection of almost all known hemoglobin disorders in an economical manner. Because this can include multiple tests for alpha-thalassemias, beta-thalassemias, delta-beta-thalassemia, hereditary persistence of fetal hemoglobin (HPFH) and for all known Hb variants, an expert in these disorders can guide testing to explain the clinical question or CBC values. This evaluation is particularly useful for complete classification of compound combinations of Hb S with alpha- or beta-thalassemia, Hb E/beta-0-thalassemia, and many other complex thalassemic disorders. Since iron deficiency can mimic thalassemias, ferritin levels are measured to evaluate this possibility.

 

Hemoglobin disorders include those associated with thalassemias (decreased protein quantity) and hemoglobin variants (abnormal protein production). Many are clinically harmless and others cause symptoms including microcytosis, sickling disorders, hemolysis, erythrocytosis, cyanosis/hypoxia, long-standing or familial anemia, compensated or episodic anemia, and increased methemoglobin or sulfhemoglobin results. Hemoglobin disorders can show autosomal recessive or autosomal dominant inheritance patterns.

 

The thalassemias are a group of disorders of hemoglobin (Hb) synthesis. Normal adult Hb consists of 2 alpha globin chains (encoded by 2 pairs of alpha globin genes, each pair located on chromosome 16), and 2 beta globin chains (encoded by 2 beta globin genes, each located on chromosome 11). Thalassemia syndromes result from an underproduction of 1 or 2 types of globin chains and are characterized by the type (alpha, beta, delta) and magnitude of underproduction (number of defective genes) and the severity of clinical symptoms (minor, intermedia, major). The severity of the clinical and hematologic effects is directly related to the imbalance of alpha-like to beta-like chains.

 

The most common form of thalassemia is alpha thalassemia. Hemoglobin H (Hb H) disease, results from dysfunction of 3 alpha chains, and shows a variable phenotype with most showing moderate anemia.

 

The deletion of all 4 alpha chains is incompatible with life. Affected fetuses are hydropic and die in utero or shortly after premature birth. The blood smears show large hypochromic red cells, nucleated red cells, target cells, and red cell fragments. Hb Barts, Hb H, and Hb Portland are present in significant quantities. It is the most common cause of hydrops fetalis in Southeast Asia and southern China.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Definitive results and an interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

A hematopathologist expert in these disorders evaluates the case, appropriate tests are performed, and an interpretive report is issued.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

DNA probe studies reveal deletional mutations that include most, but not all, alpha-thalassemias.

Clinical Reference Recommendations for in-depth reading of a clinical nature

Hoyer JD, Hoffman DR: The thalassemia and hemoglobinopathy syndromes. In Clinical Laboratory Medicine. Second edition. Edited by KD McMlatchey. Philadelphia, Lippencott Williams and Wilkins, 2002, pp 866-892

Special Instructions Library of PDFs including pertinent information and forms related to the test